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Archive - Oct 2013


October 22nd

Gene-Silencing Strategy Opens New Path to Understanding Down Syndrome

The first evidence that the underlying genetic defect responsible for trisomy 21, also known as Down syndrome, can be suppressed in laboratory cultures of patient-derived stem cells was presented today (October 22) at the opening of the American Society of Human Genetics (ASHG) 2013 annual meeting in Boston, running through October. The ASHG annual meeting is the world's largest gathering of human genetics professionals and a forum for renowned experts in the field.People with Down syndrome are born with an extra chromosome 21, which results in a variety of physical and cognitive ill effects. In laboratory cultures of cells from patients with Down syndrome, an advanced genome editing tool was successfully used to silence the genes on the extra chromosome, thereby neutralizing it, said Jeanne Lawrence, Ph.D., Professor of Cell & Developmental Biology at the University Massachusetts Medical School, Worcester, Massachusetts. Dr. Lawrence and her team compared trisomic stem cells derived from patients with Down syndrome, in which the extra chromosome 21 was silenced, to identical cells from patients that were untreated. The researchers identified defects in the proliferation, or rapid growth, of the untreated cells and the differentiation, or specialization, of untreated nervous system cells. These defects were reversed in trisomic stem cells in which the extra chromosome 21 was muted. “Silencing of trisomy 21 by manipulation of a single gene in living cells in laboratory cells surmounts the first major obstacle to development of potential ‘chromosome therapy,’” said Dr. Lawrence, whose presentation today provided an update to the results that she and her colleagues reported earlier this year in the journal Nature (Jiang et al. 2013). In her ASHG presentation, Dr.

Opportunities and Risks of Personal Genomics Are Key Topics of Sunday’s Session of the World Congress of Psychiatric Genetics in Boston

Sunday’s (October 20) portion of the five-day 2013 XXIst World Congress of Psychiatric Genetics opened with a plenary session on the “Opportunities and Risks Associated with Personal & Clinical Genomics.” The format was a panel presentation chaired by Robert C. Green, M.D., M.P.H., Associate Professor of Medicine in the Division of Genetics at Brigham and Women’s Hospital and Harvard Medical School, Associate Director for Research at Partners Health Care for Personalized Genetic Medicine, and Director of Genes2People (GTP). The four distinguished panelists were Paul Appelbaum, M.D., Professor of Psychiatry, Medicine, & Law and Director of the Division of Law, Ethics, and Psychiatry in the Department of Psychiatry at Columbia University; Atul Butte, M.D., Ph.D., Chief of the Division of Systems Medicine and Associate Professor of Pediatrics, Medicine, and Computer Science at Stanford University and Lucile Packard Children's Hospital, and a co-founder of Personalis, a contract research organization and genome-scale diagnostics services company pioneering genome-guided medicine; A. Cecile Janssens, Ph.D., Professor at Emory University in Atlanta: and Uta Francke, M.D., Professor of Genetics and Pediatrics at Stanford School of Medicine, past President of the American Society of Human Genetics, and Senior Medical Director of the personal genomics company 23andMe. Dr. Green began by discussing the purposes of genetic testing: confirmation, diagnosis of mysterious diseases, risk profiling, and research. He also stressed context: medical versus consumer interest; clinical or research; pre-conception, pre-natal, pediatric or adult; various degrees of patient education; no results and anticipated results; and incidental findings.

Identification of Over 100 Schizophrenia-Associated SNPs and Certain Autism-Associated Rare Variants Reported at World Congress of Psychiatric Genetics in Boston

Today (Monday, October 21) was the last day of the five-day 2013 XXIst World Congress of Psychiatric Genetics in Boston and the tremendous success of the meeting and the enormous progress that has recently been made were remarked upon in a comment to BioQuick by Tom Insel (photo), M.D., Director of the National Institute of Mental Health (NIMH) since 2002. “This is a rapidly moving field. Five years ago, we had too few disease-associated variants. Now, perhaps, we have too many. At this meeting, we have heard reports of the identification of over 100 schizophrenia-associated SNPs, some overlapping with bipolar disorder. This is huge. In addition, we have heard about the identification of several rare variants associated with autism and intellectual disability. This is also huge,” Dr. Insel said. Many other new and exciting discoveries were described at the Congress and virtually all of the attendees would agree with Olli Pietilainen, Ph.D., from the Institute for Molecular Medicine at the University of Finland, and presenter of his group’s identification of a gene deletion associated with schizophrenia and intellectual disability, who commented to BioQuick that this was “absolutely the best of the many psychiatric congresses I have attended.” In keeping with the extremely high quality of the entire meeting. the final day’s opening plenary session featured lively presentations and a panel discussion involving four of the world leaders in their specialties, along with interactive audience participation on two questions--(1) how the field could continue the process of genetic discovery, and (2) what are the next steps to achieve biological understanding and translation of discoveries into the clinic.

October 20th

Autism Gene Studies, PsychChip Development, and Substance Abuse Genetics Featured in Saturday Session of World Congress of Psychiatric Genetics in Boston

Day 3 (Saturday, October 19) of the XXIst World Congress of Psychiatric Genetics, taking place in Boston, began with a spectacular plenary session featuring two world-class scientists as speakers—Christopher A. Walsh, M.D., Ph.D., Bullard Professor of Psychiatry at Harvard Medical School, Chief of the Division of Genetics at Children’s Hospital Boston, and Howard Hughes Medical Institute (HHMI) Investigator, and Kevin Eggan, Ph.D., Associate Professor in the Harvard University Department of Stem Cell Biology and Regenerative Medicine, an HHMI Investigator, and an acknowledged world leader in stem cell biology. Dr. Walsh described recent results in the world-wide and genome-wide hunt for inherited genes for autism spectrum disorders (ASDs), with an emphasis on studies looking for recessive genes in consanguineous families having members with ASDs. Dr. Eggan detailed the technical difficulties in working to create pure specific brain cell type populations from human embryonic stem cells, induced pluripotent stem (iPS) cells, or transfer factor treatment of fibroblasts. While not minimizing the problems, he described progress along the road to this goal and indicated the enormous potential that success in the technical challenges will have in the study of disease mechanisms, particularly in psychiatric disorders. Dr.Walsh said that autism has an incidence of 1-2 per 1,000, while ASDs have an incidence of 6 per 1,000. ASDs have comorbidities of 50-60% with cognitive impairment, 10-25% with regression, and 30% with seizures/epilepsy suggesting that they are developmental disorders associated with abnormal brain development, he added. ASDs are highly heritable, Dr. Walsh said, and yet genetic causes have been identified for only a small fraction of the totality of the disorders.

October 18th

Biomarkers for Suicidal Behavior, Stem Cells, and Epigenetics of Cocaine Addiction Highlight Second Day of World Congress of Psychiatric Genetics in Boston

On the second day (Friday, October 18) of the XXIst World Congress of Psychiatric Genetics meeting in Boston, Alexander Niculesca, M.D., Ph.D., Associate Professor in the Department of Psychiatry at the Indiana University School of Medicine, described his group’s ground-breaking work in identifying and validating blood biomarkers for suicidal behavior, in particular the identification of a panel of six markers whose levels in the blood can help predict the risk of future hospitalizations for suicide. Dr. Niculesca emphasized the significance of these findings by noting that one million people die each year from suicide and that someone commits suicide every 40 seconds. Furthermore, the omega-3 fatty acid DHA (docosahexaenoic acid), which is a major component of the human brain, cerebral cortex, skin, sperm, testicles, and retina, can be used in the diet to reduce the suicide risk in some at-risk patients. Consequently, the ability to identify patients at high risk of suicide through simple blood tests has the potential to save lives. The most powerful predictor of the six markers in the panel was the protein coded for by the gene SAT1. SAT1 codes for the rate-limiting enzyme in the catabolic pathway of polyamine metabolism. Dr. Niculesca’s work is an example of the use of a comprehensive convergent functional genomics approach to identify risk-related genes. The results of this work were published online on August 20, 2013 in an open-access article in Molecular Psychiatry. Following Dr. Niculescu’s talk, Rakesh Karmacharya, M.D., Ph.D., Assistant Professor of Psychiatry at Harvard Medical School, described the use of induced pluripotent stem (iPS) cells that were differentiated to neuronal cells in order to look for cellular signatures of schizophrenia and bi-polar disorder in patient-derived cells.

October 17th

World Congress of Psychiatric Genetics Opens in Boston

The XXIst World Congress of Psychiatric Genetics opened today (October 17, 2013), in Boston, Massachusetts, USA, with this year’s theme being “Redefining Mental Illnesses Through Genetics.” The five-day conference, organized by the International Society of Human Genetics (ISPG), is being attended by nearly 900 of the world’s leading research and clinical experts on psychiatric diseases such as autism, schizophrenia, and major depressive disorder. Approximately 300 of these scientists have come from outside the United States. The scientists are discussing the latest developments in their fast-moving field and describing their visions of a brighter future that their work will hopefully provide, in terms of testing, treatments, and possibly even cures. On this opening day, Francis McMahon, M.D., a principal investigator at the National Institute of Mental Health, and president of the ISPG, commented to BioQuick that “the Congress program, coupled with the number and caliber of the attendees, is indicative of the steep curve of discovery in the field. With increases in sample sizes, advances in technology, and all the bright people involved, it is very likely that we will make discoveries in the next decade that will help patients and also help psychiatrists deliver better treatments.” The keynote address for the Congress was delivered by George Church, Ph.D., professor of genetics at Harvard Medical School, director of, and universally acknowledged technical wizard who has invented numerous sequencing technologies over the years and been involved in the launches of numerous biotech companies. He is also one of six scientists who proposed the new BRAIN Initiative, which was announced on April 2, 2013 by President Obama, and intends to map the activity of every neuron in the human brain. Dr.

October 14th

New Giant Viruses Discovered, Possible Missing Link between Viruses and Cells

With the discovery of Mimivirus ten years ago and, more recently, Megavirus chilensis, researchers thought they had reached the farthest corners of the viral world in terms of size and genetic complexity. With a diameter in the region of a micrometer and a genome incorporating more than 1,100 genes, these giant viruses, which infect amoebas of the Acanthamoeba genus, had already largely encroached on areas previously thought to be the exclusive domain of bacteria. For the sake of comparison, common viruses such as the influenza or HIV viruses, only contain approximately ten genes each. In an article published in the July 19, 2013 issue of Science, the researchers from France and Sweden announced they had discovered two new giant viruses: Pandoravirus salinus, on the coast of Chile, and Pandoravirus dulcis, in a freshwater pond in Melbourne, Australia. Detailed analysis has shown that these first two Pandoraviruses have virtually nothing in common with previously characterized giant viruses. What's more, only a very small percentage (6%) of the proteins encoded by Pandoravirus salinus is similar to those already identified in other viruses or cellular organisms. With a genome of this size, Pandoravirus salinus demonstrates that viruses can be more complex than some eukaryotic cells. Another unusual feature of Pandoraviruses is that they have no gene allowing them to build a protein like the capsid protein, which is the basic building block of traditional viruses. Despite all these novel properties, Pandoraviruses display the essential characteristics of other viruses in that they contain no ribosomes, produce no energy, and do not divide.

October 10th

Badgers Responsible for 50% of TB in Cattle

Badgers are ultimately responsible for roughly half of tuberculosis (TB) in cattle in areas with high TB prevalence, according to new estimates. However, only approximately six per cent of infected cattle catch TB from badgers, with onward transmission between cattle herds accounting for the remainder of TB infections, the study suggests. The findings were published online on October 10, 2013 in the open-access journal PLOS Currents: Outbreaks. The role of badgers in spreading bovine TB has been debated intensely as part of discussions about whether badgers should be culled to control the disease. The Randomized Badger Culling Trial, which ran from 1998 to 2005, found evidence that culling could reduce TB in herds inside culled areas, while increasing TB in areas nearby. Mathematical models based on data from the trial were previously used to calculate an estimate of the proportion of TB in cattle that could ultimately be attributed to transmission from badgers. The new paper, by scientists at Imperial College London, provides a more detailed analysis. It estimates that badgers ultimately account for 52 per cent of cattle TB in areas where prevalence in cattle is high. There is considerable uncertainty around this estimate, but the authors say that 38 per cent is a robust minimum value for the estimate. There is no robust maximum value. Professor Christl Donnelly, from the Medical Research Council Centre for Outbreak Analysis and Modelling at Imperial College London, said: “These findings confirm that badgers do play a large role in the spread of bovine TB.

Change in Circulating Tumor Cell Detection Has High Potential in the Prediction of Treatment Outcome in Prostate Cancer

A new study reveals that in the prediction of treatment outcome for castration-resistant prostate cancer, a change in circulating tumor cells detection might be more accurate than the change in prostate-specific antigen (PSA) levels. The findings of this award-winning study were presented at the recent EAU 13th Central European Meeting in Prague, Czech Republic ( October 4-6, 2013. "The research of the circulating tumor cells (CTC) is of utmost importance, because nowadays there is no reliable marker of both cancer-specific or overall survival in castration-resistant prostate cancer (CRPC) patients," explained the lead author of the study, Dr. Otakar Čapoun, of the Department of Urology at General Teaching Hospital Charles University in Prague, Czech Republic. "The goal of this study is to assess the possibility of the individualization of castration-resistant prostate cancer management. In cases with no favorable change in CTC detection during chemotherapy, the early switching to another therapy should be considered," commented Dr. Čapoun on the implications of the study, which was supported by the Internal Grant Agency of the Ministry of Health of the Czech Republic. Protocol of the grant project included the collection of peripheral blood from patients with metastatic CRPC prior to docetaxel therapy and after the fourth cycle of chemotherapy (CTX). Circulating tumor cells were detected by using a method of immunomagnetic separation. In the course of the study, multiplex PCR was performed after cytolysis of CTC and the expression of tumor-associated antigens (PSA, PSMA, and EGFR) was quantified. The methodology of the study was based on verbal evaluation, together with a report of the absolute values (ng/ml).

October 10th

How Microbes Can Survive Eons of Freezing Conditions

Most microbial researchers grow their cells in petri dishes to study how they respond to stress and damaging conditions. But, with the support of funding from NASA, researchers in Louisiana State University’s (LSU’s) Department of Biological Sciences tried something almost unheard of: studying microbial survival in ice to understand how microorganisms could survive in ancient permafrost, or perhaps even buried in ice on Mars. Dr. Brent Christner, associate professor of biological sciences, and colleagues at LSU including postdoctoral researcher Dr. Markus Dieser and Mary Lou Applewhite Professor John Battista, had results on DNA repair in ice-entrapped microbes published online on September 27, 2013 by the journal Applied and Environmental Microbiology. To understand how microbes survive in frozen conditions, Christner and colleagues focused on analysis of DNA, the hereditary molecule that encodes the genetic instructions used in the development and function of all organisms. “Microbes are made up of macromolecules that, even if frozen, are subject to decay,” Dr. Christner said. “We know of a range of spontaneous reactions that result in damage to DNA.” The worst kind of damage is known as a double-stranded break, where the microbe’s DNA is cleaved into two separate pieces that need to be put back together to make the chromosome functional. “This kind of damage is inevitable if cells exist frozen in permafrost for thousands of years and cannot make repairs,” Dr. Christner said. “Imagine that a microbe is in ice for extended periods of time and its DNA is progressively getting cut into pieces. There will eventually be a point when the microbe’s DNA becomes so damaged that it’s no longer a viable informational storage molecule. What is left is a corpse.” The situation would seem dire for the longevity of microbes in ice.